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. 2023 May 4;2023(5):CD013798. doi: 10.1002/14651858.CD013798.pub2

NCT00738530.

Study characteristics
Methods Study name: AVOREN
Study design: randomised, parallel, placebo‐controlled phase III
Blinding: the study was planned as a double‐blind trial, but was unblinded after a protocol amendment: quote: "An interim analysis of overall survival was prespecified after 250 deaths. On the basis of new second‐line therapies that became available while the trial was in progress, which could have confounded analyses of overall survival data, we agreed with regulatory agencies that the preplanned final analysis of progression‐free survival would be acceptable for regulatory submission." The protocol was amended to allow the study to be unblinded at this point.
Study dates: between June 2004 and October 2005 (date of enrolment)
Date of data cut‐off: September 8, 2006 for final analysis of PFS (data used in this review) and interim analysis of OS; cutoff for final analysis of OS (data used in this review) was September 2008
Location: 18 countries (Australia, Belgium, Czech Republic, Finland, France, Germany, Hungary, Israel, Italy, the Netherlands, Norway, Poland, Russian Federation, Singapore, Spain, Switzerland, Taiwan, UK., types of centres: hospitals, cancer centres (104 study locations)
Cross‐over study or cross over permitted: not per design, but cross over from the control group to receive bevacizumab was recommended for participants who had not progressed
Participants Inclusion criteria:

  • 18 years or older

  • all sexes

  • participants with measurable or non‐measurable tumour (according to RECIST criteria)

  • participants with (>50%) clear‐cell renal cell carcinoma

  • participants that have undergone nephrectomy or partial nephrectomy

  • KPS ≥ 70%


Exclusion criteria:

  • prior systemic treatment for metastatic RCC

  • recent major surgical procedures

  • evidence of brain metastases

  • ongoing need for full dose anticoagulants

  • uncontrolled hypertension

  • clinically significant cardiovascular disease.


Sample size: N = 649
Age (years, median with range): experimental arm: 61 (30‐82), control arm: 60 (18‐81)
Sex (m/f): experimental arm: 222/10, control arm: 234/88
Prognostic factors:

  • MSKCC risk score

    • Favourable

      • experimental arm: 87 (27), control arm: 93 (29)

    • Intermediate

      • experimental arm: 183 (56), control arm: 180 (56)

    • Poor

      • experimental arm: 29 (9), control arm: 5 (8)

    • Not available

      • experimental arm: 28 (9), control arm: 24 (7)

  • Previous nephrectomy (n,%)

    • Yes

      • (all participants)
Interventions Experimental arm (n = 327): Bevacizumab (10mg/kg, intravenous, every two weeks + IFN‐alfa (9 MIU, subcutaneous injection, thrice/week)
Control arm (n = 322): Placebo + IFN‐a (9 MIU, subcutaneous injection, thrice/week)
Outcomes Primary outcome(s)

  • OS


Secondary outcome(s)

  • PFS

  • Safety (AE/SAE)

  • Number of participants who discontinued treatment due to an AE


Relevant to this review but not reported: QoL, TFST
Other outcomes (not relevant to this review): ORR, OR, CR, TTF, TTP
Notes Funding sources: Alain Ravaud, F. Hoffmann‐La Roche, GlaxoSmithKline
Declarations of Interests: Quote: "Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article(...), please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in
Information for Contributors."
Clinical study report available: no
Study protocol available: no
Statistical analysis plan available: no